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. 1990 Dec;101(4):799–802. doi: 10.1111/j.1476-5381.1990.tb14160.x

Enhancement of the endothelial production of prostacyclin by inhibitors of protein synthesis.

J M Boeynaems 1, O Boutherin-Falson 1, C Lagneau 1, N Galand 1
PMCID: PMC1917833  PMID: 2128194

Abstract

1. Pretreatment of bovine aortic endothelial cells with cycloheximide enhanced their capacity to release prostacyclin in response to adenosine 5'-triphosphate (ATP) and bradykinin. 2. The action of cycloheximide was time-dependent; it became detectable after a 1 h exposure to the cells and was maximal after 3 h. 3. Puromycin mimicked the effect of cycloheximide. For these two agents, the enhancement of prostacyclin release was obtained at concentrations producing a partial inhibition of protein synthesis. 4. Cycloheximide increased the mobilization of free arachidonic acid induced by ATP in bovine aortic endothelial cells. 5. In conclusion, the synthesis of new proteins is not involved in the stimulatory action of ATP and bradykinin on prostacyclin production by bovine aortic endothelial cells. Despite the short half-life of prostaglandin H synthase in endothelial cells, cycloheximide and puromycin enhanced the release of prostacyclin induced by agonists. Our data suggest that this release might be under the control of rapidly turning-over phospholipase inhibitory proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boeynaems J. M., Galand N., Ketelbant P. Prostacyclin production by the deendothelialized rabbit aorta. J Clin Invest. 1985 Jul;76(1):7–14. doi: 10.1172/JCI111979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Booyse F. M., Sedlak B. J., Rafelson M. E., Jr Culture of arterial endothelial cells: characterization and growth of bovine aortic cells. Thromb Diath Haemorrh. 1975 Dec 15;34(3):825–839. [PubMed] [Google Scholar]
  3. Carter T. D., Hallam T. J., Cusack N. J., Pearson J. D. Regulation of P2y-purinoceptor-mediated prostacyclin release from human endothelial cells by cytoplasmic calcium concentration. Br J Pharmacol. 1988 Dec;95(4):1181–1190. doi: 10.1111/j.1476-5381.1988.tb11754.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cavender D., Haskard D., Foster N., Ziff M. Superinduction of T lymphocyte-endothelial cell (EC) binding by treatment of EC with interleukin 1 and protein synthesis inhibitors. J Immunol. 1987 Apr 1;138(7):2149–2154. [PubMed] [Google Scholar]
  5. Clark M. A., Littlejohn D., Conway T. M., Mong S., Steiner S., Crooke S. T. Leukotriene D4 treatment of bovine aortic endothelial cells and murine smooth muscle cells in culture results in an increase in phospholipase A2 activity. J Biol Chem. 1986 Aug 15;261(23):10713–10718. [PubMed] [Google Scholar]
  6. Clark M. A., Littlejohn D., Mong S., Crooke S. T. Effect of leukotrienes, bradykinin and calcium ionophore (A 23187) on bovine endothelial cells: release of prostacyclin. Prostaglandins. 1986 Jan;31(1):157–166. doi: 10.1016/0090-6980(86)90233-9. [DOI] [PubMed] [Google Scholar]
  7. Colden-Stanfield M., Schilling W. P., Ritchie A. K., Eskin S. G., Navarro L. T., Kunze D. L. Bradykinin-induced increases in cytosolic calcium and ionic currents in cultured bovine aortic endothelial cells. Circ Res. 1987 Nov;61(5):632–640. doi: 10.1161/01.res.61.5.632. [DOI] [PubMed] [Google Scholar]
  8. Davidson F. F., Dennis E. A., Powell M., Glenney J. R., Jr Inhibition of phospholipase A2 by "lipocortins" and calpactins. An effect of binding to substrate phospholipids. J Biol Chem. 1987 Feb 5;262(4):1698–1705. [PubMed] [Google Scholar]
  9. Derian C. K., Moskowitz M. A. Polyphosphoinositide hydrolysis in endothelial cells and carotid artery segments. Bradykinin-2 receptor stimulation is calcium-independent. J Biol Chem. 1986 Mar 15;261(8):3831–3837. [PubMed] [Google Scholar]
  10. Fagan J. M., Goldberg A. L. Inhibitors of protein and RNA synthesis cause a rapid block in prostaglandin production at the prostaglandin synthase step. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2771–2775. doi: 10.1073/pnas.83.8.2771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hullin F., Raynal P., Ragab-Thomas J. M., Fauvel J., Chap H. Effect of dexamethasone on prostaglandin synthesis and on lipocortin status in human endothelial cells. Inhibition of prostaglandin I2 synthesis occurring without alteration of arachidonic acid liberation and of lipocortin synthesis. J Biol Chem. 1989 Feb 25;264(6):3506–3513. [PubMed] [Google Scholar]
  12. Lambert T. L., Kent R. S., Whorton A. R. Bradykinin stimulation of inositol polyphosphate production in porcine aortic endothelial cells. J Biol Chem. 1986 Nov 15;261(32):15288–15293. [PubMed] [Google Scholar]
  13. Maclouf J. A radioimmunoassay for 6-keto-PGF1 alpha. Methods Enzymol. 1982;86:273–286. doi: 10.1016/0076-6879(82)86200-9. [DOI] [PubMed] [Google Scholar]
  14. Morgan-Boyd R., Stewart J. M., Vavrek R. J., Hassid A. Effects of bradykinin and angiotensin II on intracellular Ca2+ dynamics in endothelial cells. Am J Physiol. 1987 Oct;253(4 Pt 1):C588–C598. doi: 10.1152/ajpcell.1987.253.4.C588. [DOI] [PubMed] [Google Scholar]
  15. Raz A., Wyche A., Needleman P. Temporal and pharmacological division of fibroblast cyclooxygenase expression into transcriptional and translational phases. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1657–1661. doi: 10.1073/pnas.86.5.1657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. SIEKEVITZ P. Uptake of radioactive alanine in vitro into the proteins of rat liver fractions. J Biol Chem. 1952 Apr;195(2):549–565. [PubMed] [Google Scholar]
  17. Van Coevorden A., Boeynaems J. M. Physiological concentrations of ADP stimulate the release of prostacyclin from bovine aortic endothelial cells. Prostaglandins. 1984 Apr;27(4):615–626. doi: 10.1016/0090-6980(84)90097-2. [DOI] [PubMed] [Google Scholar]
  18. Wickramasinghe J. A., Morozowich W., Hamlin W. E., Shaw S. R. Detection of prostaglandin F2 alpha as pentafluorobenzyl ester by electron-capture GLC. J Pharm Sci. 1973 Sep;62(9):1428–1431. doi: 10.1002/jps.2600620906. [DOI] [PubMed] [Google Scholar]
  19. Willems C., De Groot P. G., Pool G. A., Gonsalvez M. S., Van Aken W. G., Van Mourik J. A. Arachidonate metabolism in cultured human vascular endothelial cells. Evidence for two prostaglandin synthetic pathways sensitive to acetylsalicylic acid. Biochim Biophys Acta. 1982 Dec 13;713(3):581–588. doi: 10.1016/0005-2760(82)90318-6. [DOI] [PubMed] [Google Scholar]
  20. Wu K. K., Hatzakis H., Lo S. S., Seong D. C., Sanduja S. K., Tai H. H. Stimulation of de novo synthesis of prostaglandin G/H synthase in human endothelial cells by phorbol ester. J Biol Chem. 1988 Dec 15;263(35):19043–19047. [PubMed] [Google Scholar]

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